shogaol and Colorectal-Neoplasms

Topics: Adenoma; Animals; Anti-Inflammatory Agents; Antioxidants; Azoxymethane; Colonic Neoplasms; Colorectal Neoplasms; Disease Models, Animal; Inflammation; Male; Mice

Leukotriene A4 hydrolase (LTA

Topics: Aminopeptidases; Antineoplastic Agents; Catechols; Cell Proliferation; Colorectal Neoplasms; Dose-Response Relationship, Drug; Enzyme Inhibitors; Epoxide Hydrolases; Fatty Alcohols; Humans; Molecular Docking Simulation; Molecular Structure; Recombinant Proteins; Structure-Activity Relationship; Tumor Cells, Cultured

6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death. After 24h, cell shrinkage and Caspase-3/7 activities rising, suggesting that apoptotic cell death had increased. And after 48h, the result of TUNEL assay indicated the highest occurrence of apoptosis upon 6-shogaol treatment. It appeared that apoptosis is triggered by autophagy in 6-shogaol treated HT-29 cells, the damage of autophagic cell death initiated apoptosis program.

Topics: Adenocarcinoma; Apoptosis; Autophagy; Caspase 3; Caspase 7; Catechols; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Colorectal Neoplasms; G2 Phase Cell Cycle Checkpoints; HT29 Cells; Humans; Reactive Oxygen Species; Signal Transduction; Zingiber officinale

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21(waf1/cip1) and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53(-/-) and p53(+/+) HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

Topics: Animals; Apoptosis; Catechols; CDC2 Protein Kinase; cdc25 Phosphatases; Cell Proliferation; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Disease Models, Animal; Dose-Response Relationship, Drug; Female; G2 Phase Cell Cycle Checkpoints; Gene Expression; Heterografts; Humans; Mice, Nude; Neoplasm Transplantation; Phytotherapy; Receptor Cross-Talk; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Up-Regulation

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anticarcinogenic properties. This study examined the growth inhibitory effects of the structurally related compounds 6-gingerol and 6-shogaol on human cancer cells. 6-Shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one] inhibits the growth of human cancer cells and induces apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of 6-shogaol-induced apoptosis, preceding cytochrome c release, caspase activation, and DNA fragmentation. Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.

Topics: Adenocarcinoma; Apoptosis; Caspases; Catechols; Cell Line, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Fatty Alcohols; Humans; Membrane Potentials; Mitochondrial Membranes; Plant Extracts; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Transcription Factor CHOP; Zingiber officinale